Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults
HIV, HIV Infections, Acquired Immunodeficiency Syndrome
About this trial
This is an interventional treatment trial for HIV focused on measuring HIV-1, HIV, Treatment-Experienced
Eligibility Criteria
Key Inclusion Criteria:
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- Currently taking a failing ARV regimen
- Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
- Normal ECG
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
- Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Adequate hematologic function
- Serum amylase ≤ 5 × ULN
Females may enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation [for ≥ 12 months] of previously occurring menses), or
Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following study drug dosing
- Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
- Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
- Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
Key Exclusion Criteria:
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Hepatitis B surface antigen (HBsAg) positive
- Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll)
- History of integrase inhibitor use
- Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.
- Screening or historical genotype report shows resistance to integrase inhibitors
- Individuals experiencing decompensated cirrhosis
- Current alcohol or substance use
- History of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Part 1, Day 1 and must not be anticipated to require systemic therapy during the study.
- Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Part 1, Day 1
- Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements
- Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
- Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Midway Immunology and Research center
- Triple O Research Institute, P.A.
- Rowan Tree Medical, P.A.
- Wake Forest University Health Sciences
- Penn Presbyterian Medical Center
- Salvador B Gautier Hospital - Infectious Diseases Department
- Instituto Dominicano de Estudio Virologicos - IDEV
- Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS
- Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg
- The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
- Ramathibodi Hospital, Mahidol University
- Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine
- Chiang Mai University
- Khon Kaen University
- Joint Clinical Research Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Placebo Comparator
Experimental
Part 1 Sentinel Cohort (TAF)
Part 1 Randomized Cohort (TAF)
Part 1 Randomized Cohort (Placebo)
Part 2 E/C/F/TAF+ATV
TAF + their current failing ARV regimen for 10 days in Part 1
Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1.
Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1.
Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a > 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.